Diseases that cause weakness in muscles include sarcopenia, which progresses with aging; muscular atrophy, which is caused by an imbalance in protein metabolism and a decrease in muscle use; and acardiotrophy, which progresses with starvation, debilitating diseases (cancer, etc.), and aging.
Sarcopenia refers to a reduction in muscle strength due to a decrease in skeletal muscle mass while aging is in progress. The decrease in skeletal muscle mass, which is the most important characteristic of sarcopenia, and additionally the changes in the types of muscle fibers are observed together. Whereas the diameters of Type 1 and Type 2 muscle fibers decrease at a similar rate as aging progresses, under sarcopenia, the diameter of the Type 2 muscle fiber does not change significantly, but the diameter of the Type 1 muscle fiber noticeably decreases. It has been reported that sarcopenia causes senility and functional disorders that occur among the elderly.
Sarcopenia is caused by various factors, but studies regarding each factor are still in progress. Sarcopenia is induced by a reduction in the growth hormone level or neurological changes, changes in physiological activity, changes in metabolism, an increase in the amount of sex hormones or fat and catabolic cytokines, and a change in the balance of protein synthesis and degradation. The most important cause of the decrease in skeletal muscle mass, which is the most pronounced characteristic of sarcopenia, is known to be the reduction of satellite cell activation. Satellite cells are small mononuclear cells located between a basement membrane and a sarcolemma of muscle fibers. These satellite cells are activated by stimuli such as injury or exercise and are proliferated as myoblasts, and as the differentiation is in progress, they fuse with other cells to form multinucleated muscle fibers. Accordingly, as the satellite cell activation is reduced, the ability to regenerate a damaged muscle or responses to differentiation signals is reduced, thereby resulting in a decrease in the muscle formation.
Muscular atrophy is caused by nutritional deficiency or after a long period of physical inactivity, and it is indicated by protein degradation which occurs due to a disruption in the balance between protein synthesis and degradation.
On the other hand, acardiotrophy is caused by starvation, debilitating diseases (cancer, etc.), and senility, myocardial fibers become thinner, and the nucleus becomes concentrated and exhibits anisocytosis. As a result, the volume of muscle fascicles is decreased, the heart as a whole becomes smaller, the size of subepicardial adipose tissues is clearly decreased, and coronary arteries become curved. A consumable dye (lipofuscin) appears at both ends of the nucleus of myocardial fibers as a brown dye, and along with the reduction of adipose tissues, the entire heart displays a brown color.
The treatment methods for sarcopenia include three methods. The first method is exercise. Exercise improves, in the short term, the ability of the protein synthesis of skeletal muscles, and it has been reported to increase muscle strength and mobility in the elderly. However, exercise is not appropriate as a long-term treatment method. The second method is, as a drug treatment, the administration of testosterone or anabolic steroids, but this induces masculinization in females, and in males, side effects such as prostate symptoms may occur. For the other approved method, dehydroepiandrosterone (DHEA) and growth hormones are available, and a study was reported that it is possible to apply these as a treatment method at a region including selective androgen receptor modulators (SARMs) (D. D. Thompson, J. Musculoskelet Neuronal Interact 7, 344-345, 2007). In particular, although diet has been known as a treatment method, malnutrition and modern eating habits are inappropriate for maintaining the proper total body mass, according to a nutritional assessment.
Recently, stem cell therapy, in which satellite cells are isolated and differentiated in vitro so that they are introduced into the body, and the method for directly activating satellite cells in the body to promote myogenesis in order to maintain or strengthen the muscle are being highlighted as possible treatment methods for treating muscle weakness such as sarcopenia (Shihuan Kuang, and Michael A. Rudnicki, Trends in Molecular Medicine 14, 82-31, 2008).
Therefore, in order to treat diseases associated with muscle weakness, a method for differentiating myoblasts is demanded as a more fundamental method without side effects, and as a result, the development of a substance capable of promoting the differentiation of myoblasts is highly necessary.